It is proposed to intervene pharmacologically in the biochemistry of cone photoreceptors and to assess this intervention electrophysiologically. The goal is to identify enzyme systems present in cones which may be involved in excitation and/or adaptation. If a chemical effects the excitation or adaptation process, then if must modulate the membrane permeability or photoreceptor sensitivity in a manner similar to light or darkness. Based on previous work, suspect enzyme systems are phosphodiesterase which hydrolyzes cyclic nucleotides, cyclase which synthesizes cyclic nucletides and kinase which phosphorylates proteins. Specific inhibitors, activators or substrates of these enzymes will be applied to ascertain which modify photoreception. The chemicals will be applied when possible by intracellular injection into cones in the perfused, isolated, sliced preparation of the turtle retina. Cones will be impaled by double-barreled electrodes under visual control using an infrared television system. The effects of the application of these chemicals will be assessed by monitoring the membrane potential and sensitivity of the cone to see which mimic changes in the level of illumination. If the agent modulates potential, then the accompanying conductance change will be measured, the reversal potential determined, and ion substitution studies performed. The result of these studies should indicate that the same ionic channels that are modulated by changes in illumination are involved in the chemical intervention. If the agent modulates the sensitivity of cones, then the speed of response of the system will be measured. For example, to play a meaningful role in sensitivity control, the speed of response should show equal increases for equal decreases in sensitivity regardless of whether these decreases are caused by light or by the application of the pharmacological agent. Similarly, the time course of sensitivity changes will be compared.